Department of Neurology, University of Alabama at Birmingham (UAB), Heersink School of Medicine, Birmingham, AL, USA.
Department of Neurology, University of Alabama at Birmingham (UAB), Heersink School of Medicine, Birmingham, AL, USA; Departments of Neurobiology and Neurosurgery, University of Alabama at Birmingham (UAB), Heersink School of Medicine, Birmingham, AL, USA.
Neuroimage Clin. 2023;39:103462. doi: 10.1016/j.nicl.2023.103462. Epub 2023 Jun 27.
Neuroinflammation may contribute to the pathophysiology of psychogenic non-epileptic seizures (PNES). However, it is unclear whether and to what degree comorbid psychiatric symptoms explain this association. In this study, we investigated the neuroinflammatory signature of PNES and how it compares to that of people with psychiatric conditions (PwPCs).
We prospectively assessed differences in neurite density (NDI), orientation dispersion (ODI), and isotropic diffusion (F-ISO) in 23 participants with PNES and 27 PwPCs, and their relationships to serum levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1 using voxelwise multiple linear regressions. Pearson correlations between serum biomarkers and clinical symptoms were also obtained.
There were no white matter (WM) microstructural differences between groups. In PNES, TNF-R1 was negatively associated with NDI in the right uncinate fasciculus (UF) and positively associated with F-ISO in the left UF. IL-6 was positively associated with NDI and negatively with F-ISO in the left UF. ICAM-1 was positively associated with ODI in the left UF. TNF-α was negatively associated with ODI in the left cingulum bundle. The opposite relationships were observed in PwPCs. Higher TNF-R1 was associated with higher depression, anxiety, lower emotional quality of life, and higher levels of disability in PNES.
For the first time, we report relationships between peripheral inflammatory biomarkers and WM integrity in PNES, including abnormalities in the UF and cingulum bundle. Our results suggest that serum biomarkers of inflammation may, with additional studies, become a useful aid to PNES diagnosis, especially in settings where video-EEG is not available. The lack of group differences in WM microstructure suggests that previously identified WM abnormalities in PNES versus healthy controls may be related to psychological comorbidities of PNES.
神经炎症可能导致心因性非癫痫性发作（PNES）的病理生理学变化。然而，目前尚不清楚共病精神症状是否以及在何种程度上解释了这种关联。在这项研究中，我们研究了 PNES 的神经炎症特征，以及其与患有精神疾病（PwPCs）的人群的神经炎症特征有何不同。
我们前瞻性地评估了 23 名 PNES 患者和 27 名 PwPCs 的神经突密度（NDI）、方向分散（ODI）和各向同性扩散（F-ISO）差异，并使用体素多元线性回归分析了它们与肿瘤坏死因子（TNF）-α、TNF 受体 1（TNF-R1）、TNF 相关凋亡诱导配体（TRAIL）、白细胞介素（IL）-6、细胞间黏附分子（ICAM）-1 和单核细胞趋化蛋白（MCP）-1 血清水平之间的关系。还获得了血清生物标志物与临床症状之间的 Pearson 相关性。
两组之间的白质（WM）微观结构没有差异。在 PNES 中，TNF-R1 与右侧钩束的 NDI 呈负相关，与左侧钩束的 F-ISO 呈正相关。IL-6 与左侧钩束的 NDI 呈正相关，与 F-ISO 呈负相关。ICAM-1 与左侧 UF 的 ODI 呈正相关。TNF-α与左侧扣带束的 ODI 呈负相关。在 PwPCs 中观察到相反的关系。在 PNES 中，较高的 TNF-R1 与较高的抑郁、焦虑、较低的情绪生活质量和较高的残疾水平相关。
这是首次报道 PNES 中外周炎症生物标志物与 WM 完整性之间的关系，包括 UF 和扣带束的异常。我们的结果表明，炎症的血清生物标志物可能会随着进一步的研究，成为 PNES 诊断的有用辅助手段，特别是在没有视频-EEG 的情况下。WM 微观结构的组间差异不明显表明，PNES 与健康对照组之间先前确定的 WM 异常可能与 PNES 的心理共病有关。
